Polypyridyl ruthenium complexes as novel photosensitizers had drawn attention due to its high selectivity towards cancer cells and low toxicity to normal cells. Herein, we synthesized a lysosome-targeted polypyridyl ruthenium complex Rhein-Ru(bpy)₃ (bpy = 2,2′-bipyridine, rhein = 4,5-dihydroxy-9,10-dioxoanthracene-2-carboxylic acid), tethering with the Chinese medicine herb rhein. Rhein-Ru(bpy)₃ exhibited high phototoxicity with short time of irradiation against tumor cell lines with the IC₅₀ value of 2.4– 8.7 μM, and higher cytotoxicity against cisplatin-resistant A2780 cell lines, suggesting that Rhein-Ru(bpy)₃ could overcome the cisplatin resistance. Moreover, Rhein-Ru(bpy)₃ displayed low cytotoxicity towards cell lines in dark incubation, which was beneficial to reduce the toxic side effects towards normal cell lines. Besides, the confocal imaging and western blotting assay results suggested that Rhein-Ru(bpy)₃ could induce cancer cell death through the autophagy pathway. These results inspired us that lysosome-targeted photosensitizers based on ruthenium complexes showed great potential for photodynamic therapy (PDT) application in cancer treatment.

聚吡啶基钌配合物作为新型光敏剂，因其对癌细胞的高选择性和对正常细胞的低毒性而备受关注。在这里，我们合成了靶向溶酶体的聚吡啶钌钌配合物Rhein-Ru（bpy）₃（bpy = 2,2'-联吡啶，大黄酸= 4,5-二羟基-9,10-二氧代蒽-2-羧酸），与中药大黄酸。Rhein-Ru（bpy）₃对肿瘤细胞系具有短时照射的高光毒性，IC ₅₀值为2.4-8.7μM，对顺铂耐药的A2780细胞系具有更高的细胞毒性，表明Rhein-Ru（bpy）₃可以克服顺铂耐药性。此外，Rhein-Ru（bpy）_图3显示了在黑暗温育中对细胞系的低细胞毒性，这有利于减少对正常细胞系的毒性副作用。此外，共聚焦成像和蛋白质印迹分析结果表明， Rhein-Ru（bpy）₃可以通过自噬途径诱导癌细胞死亡。这些结果启发了我们，基于钌配合物的以溶酶体为靶标的光敏剂在光动力疗法（PDT）在癌症治疗中的应用显示出巨大的潜力。